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槲皮素通过抑制实验性近视中 PERK-EIF2α 轴减轻巩膜重塑。

Quercetin Alleviates Scleral Remodeling Through Inhibiting the PERK-EIF2α Axis in Experiment Myopia.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, China.

Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):11. doi: 10.1167/iovs.65.13.11.

Abstract

PURPOSE

This study aims to investigate the effect of quercetin (QUE) on scleral remodeling by inhibiting the PERK-EIF2α signaling pathway and to evaluate its potential role in slowing myopia.

METHODS

Lens-induced myopia (LIM) guinea pigs were obtained and treated with QUE. After 4 and 6 weeks of treatments, ocular biological measurements were conducted. Hematoxylin and eosin (H&E) staining was used to observe the changes in scleral morphology and thickness, and Masson staining was used to examine scleral collagen fiber arrangement. Quantitative PCR (qPCR) and Western bolt were utilized to detect the mRNA and protein expression of PERK, EIF2α, MMP-2, TIMP-2, and collagen I in the scleral tissues. Calcium ion flow in each group was measured using noninvasive micro-test technology, and reactive oxygen species levels were detected by flow cytometry.

RESULTS

Compared with the LIM group, the ocular measurements showed that the refractive errors and axial length of the eyes were significantly reduced in the LIM + QUE group (P < 0.01). H&E and Masson staining showed that sclera in the LIM + QUE group was thickened, collagen was dense, and the fiber gap was reduced. In the LIM + QUE group, the expression levels of PERK, EIF2α, and MMP-2 were decreased, whereas the expression levels of TIMP-2 and collagen I were increased. Calcium release and reactive oxygen species (ROS) in the LIM + QUE group were decreased.

CONCLUSIONS

Quercetin ameliorates scleral remodeling in myopic guinea pigs by inhibiting the PERK-EIF2α signaling pathway, thereby alleviating the progression of myopia. These findings provide new experimental evidence for the potential application of quercetin in myopia prevention and treatment.

摘要

目的

本研究旨在通过抑制 PERK-EIF2α 信号通路来研究槲皮素(QUE)对巩膜重塑的影响,并评估其在减缓近视中的潜在作用。

方法

建立鸡眼球晶状体诱导型近视(LIM)模型,并用 QUE 进行处理。在治疗 4 周和 6 周后,进行眼部生物学测量。使用苏木精和伊红(H&E)染色观察巩膜形态和厚度的变化,使用 Masson 染色观察巩膜胶原纤维排列。利用实时定量聚合酶链反应(qPCR)和 Western blot 检测巩膜组织中 PERK、EIF2α、MMP-2、TIMP-2 和胶原 I 的 mRNA 和蛋白表达。利用非侵入性微测试技术测量各组钙离子流,通过流式细胞术检测活性氧(ROS)水平。

结果

与 LIM 组相比,LIM+QUE 组的眼屈光不正和眼轴明显减小(P<0.01)。H&E 和 Masson 染色显示,LIM+QUE 组巩膜增厚,胶原致密,纤维间隙减小。在 LIM+QUE 组中,PERK、EIF2α 和 MMP-2 的表达水平降低,而 TIMP-2 和胶原 I 的表达水平升高。LIM+QUE 组钙离子释放和活性氧(ROS)减少。

结论

槲皮素通过抑制 PERK-EIF2α 信号通路改善近视豚鼠的巩膜重塑,从而减缓近视的进展。这些发现为槲皮素在近视预防和治疗中的潜在应用提供了新的实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b55/11549929/5a5f2aa02917/iovs-65-13-11-f001.jpg

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